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Estimation With Cox Models: Cause-specific Survival Analysis With Misclassified Cause of Failure

Van Rompaye, Barta; Jaffar, Shabbarb; Goetghebeur, Elsa

doi: 10.1097/EDE.0b013e3182454cad
Survival

While epidemiologic and clinical research often aims to analyze predictors of specific endpoints, time-to-the-specific-event analysis can be hampered by problems with cause ascertainment. Under typical assumptions of competing risks analysis (and missing-data settings), we correct the cause-specific proportional hazards analysis when information on the reliability of diagnosis is available. Our method avoids bias in effect estimates at low cost in variance, thus offering a perspective for better-informed decision making. The ratio of different cause-specific hazards can be estimated flexibly for this purpose. It thus complements an all-cause analysis. In a sensitivity analysis, this approach can reveal the likely extent and direction of the bias of a standard cause-specific analysis when the diagnosis is suspect. These 2 uses are illustrated in a randomized vaccine trial and an epidemiologic cohort study, respectively.

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From the aDepartment of Applied Mathematics and Computer Science, Ghent University, Ghent, Belgium; and bFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Submitted 21 January 2011; accepted 4 November 2011.

Supported by the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT-Vlaanderen) through a research fellowship (B.V.R.). E.G. acknowledges support from the IAP research network grant nr. P06/03 from the Belgian government (Belgian Science Policy). The authors reported no other financial interests related to this research.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com). This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Bart Van Rompaye, Department of Applied Mathematics and Computer Science WE02, Ghent University, Krijgslaan 281, S9, 9000 Ghent, Belgium. E-mail: bart.vanrompaye@ugent.be.

© 2012 Lippincott Williams & Wilkins, Inc.